Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 muM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Vairano, M., Graziani, G., Tentori, L., Tringali, G., Navarra, P., Dello Russo, C. (2004). Primary cultures of microglial cells for testing toxicity of anticancer drugs. TOXICOLOGY LETTERS, 148, 91-94 [10.1016/j.toxlet.2003.12.058].

Primary cultures of microglial cells for testing toxicity of anticancer drugs

GRAZIANI, GRAZIA;TENTORI, LUCIO;
2004-01-01

Abstract

Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 muM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
antineoplastic agent; bacterium lipopolysaccharide; methotrexate; temozolomide; animal cell; article; brain cortex; brain tumor; cell activation; cell culture; cell metabolism; cell viability; controlled study; drug cytotoxicity; microglia; neurotoxicity; nonhuman; priority journal; rat; statistical significance; Animals; Animals, Newborn; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Cell Culture Techniques; Cell Survival; Dacarbazine; Drug Screening Assays, Antitumor; Humans; Lipopolysaccharides; Methotrexate; Microglia; Nervous System Diseases; Rats; Rats, Wistar; Toxicity Tests; Bacteria (microorganisms)
Vairano, M., Graziani, G., Tentori, L., Tringali, G., Navarra, P., Dello Russo, C. (2004). Primary cultures of microglial cells for testing toxicity of anticancer drugs. TOXICOLOGY LETTERS, 148, 91-94 [10.1016/j.toxlet.2003.12.058].
Vairano, M; Graziani, G; Tentori, L; Tringali, G; Navarra, P; Dello Russo, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/40973
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